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Trial details
A study of the Efficacy and Safety of SHP647 as Induction Therapy in Subjects with Moderate to Severe Ulcerative Colitis
Current status:
Approved
|
Date registered:
23/10/2019
|
Date last updated:
23/09/2019
Trial version(s)
History: 27/05/2019
Current: 27/05/2019
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2019090238
Protocol number
SHP647-302
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
Primary sponsor
Shire Human Genetic Therapies, Inc. ("Shire")
Primary sponsor: Country of origin
USA
Public title
A study of the Efficacy and Safety of SHP647 as Induction Therapy in Subjects with Moderate to Severe Ulcerative Colitis
Acronym
FIGARO UC 302
Scientific title
A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects with Moderate to Severe Ulcerative Colitis
Acronym
FIGARO UC 302
Brief summary of the study: English
The purpose of this study, which involves research, is to determine whether an investigational drug, SHP647, is safe and effective in the treatment of moderate to severe UC, compared with placebo (dummy treatment)
Brief summary of the study: Arabic
(امنا و فعالا لعلاج التهاب القولون التقرحي المعتدل الى الحاد مقارنة بدواء وهمي (علاج غير فعال SHP647 الهدف من هذه الدراسة هو تحديد ما اذا كان الدواء البحثي
Health conditions/problem studied: Specify
Moderate to severe Ulcerative Colitis
Interventions: Specify
The study consists of a screening period up to 6 weeks and a 12-week treatment period. After the screening period, eligible subjects will be randomly assigned to receive 1 of 3 treatments (25 mg SHP647, 75 mg SHP647, or placebo) in a 2:2:1 ratio. Randomization will be stratified based upon the subject’s status of prior anti-tumor necrosis factor (TNF) treatment (naïve or experienced) and glucocorticoid use at baseline (on glucocorticoids at baseline versus not on glucocorticoids at baseline). Subjects will receive SC injections of SHP647 or placebo, using a prefilled syringe (PFS), on Week 0/Day 1 (Visit 2), Week 4 (Visit 4), and Week 8 (Visit 5). Subjects will undergo efficacy, biomarker, PK, safety, and health outcome assessments at these visits At the end of the 12-week treatment period, eligible subjects will be offered the opportunity to participate in a double-blind maintenance study (SHP647-303; for subjects who achieve clinical response) or a long-term safety extension (LTS) study (SHP647-304; for subjects who do not achieve a clinical response). Subjects who withdraw early from the 12-week treatment period or who do not wish to enter the maintenance study (SHP647-303) or LTS study (SHP647-304) will continue into a 16-week safety follow-up period. Only those subjects who complete the full course of investigational product treatment in the induction studies (SHP647-302) will be eligible to continue in the maintenance study or LTS study.
Key inclusion and exclusion criteria: Inclusion criteria
1. Subjects and/or their parent or legally authorized representative must have an understanding, ability, and willingness to fully comply with study procedures and restrictions. 2. Subjects must be able to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent and/or assent, as applicable, to participate in the study. 3. Subjects must be between ≥16 and ≤80 years of age at the time of the signing of the informed consent/assent form (for Lebanon must be ≥ 18 and ≤80 years of age). NOTE: Subjects <18 years of age must weigh ≥40 kg and must have body mass index (BMI) ≥16.5. (NA for Lebanon) 4. Subjects must have a documented diagnosis (radiologic or endoscopic with histology) of UC for ≥ 3 months before screening. The following must be available in each subject’s source documentation: • A biopsy report to confirm the histological diagnosis. • A report documenting disease duration based upon prior colonoscopy. NOTE: If this documentation is not available at the time of screening, a colonoscopy with biopsy to confirm the diagnosis is required during the screening period. 5. Subjects must be willing to undergo a flexible sigmoidoscopy or colonoscopy (if preferred), including biopsy sample collection, during screening after all other inclusion criteria have been met. 6. Subjects must have moderate to severe active UC, defined as a total Mayo score of ≥ 6, including a centrally read endoscopic subscore ≥ 2, rectal bleeding subscore ≥1, and stool frequency subscore ≥ 1 at baseline (Visit 2). 7. Subjects must have evidence of UC extending proximal to the rectum (ie, not limited to proctitis). 8. Subjects must have had an inadequate response to, or lost response to, or had an intolerance to at least 1 conventional treatment such as mesalamine (5-ASA), glucocorticoids, immunosuppressants (azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]), or anti-TNF (refer to Appendix 4 for guidance). 9. Subjects receiving any treatment(s) for UC described in Section 5.2.1 of the protocol are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time. 10. Subjects are males or nonpregnant, nonlactating females who, if sexually active, agree to comply with the contraceptive requirements of the protocol, or females of nonchildbearing potential. Males and females of reproductive potential who are sexually active must agree to use appropriate contraception for the duration of the study.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
80
Key inclusion and exclusion criteria: Exclusion criteria
1. Subjects with indeterminate colitis, microscopic colitis, non-steroidal anti-inflammatory drug-induced colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of Crohn’s disease. 2. Subjects with colonic dysplasia or neoplasia. (Subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed.) 3. Subjects with past medical history or presence of toxic megacolon. 4. Subjects with colonic stricture, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for UC during the treatment period. 5. Subjects at risk for colorectal cancer must have a colonoscopy (Eaden and Mayberry 2002) performed during the screening period with results available within 10 days before the baseline visit (Visit 2), unless the subject has had a surveillance colonoscopy performed within 1 year prior to screening, and any adenomatous polyps found at that examination have been excised. Colonoscopy report and pathology report (if biopsies are obtained) from the colonoscopy performed during screening or in the prior year confirming no evidence of dysplasia and colon cancer must be available in the source documents. Subjects at risk for colorectal cancer include, but are not limited to: • Subjects with extensive colitis for ≥8 years or disease limited to left side of colon (ie, distal to splenic flexure) for ≥10 years before screening, regardless of age. • Subjects ≥50 years of age at the time of signing of the informed consent form. 6. Subjects have had prior treatment with SHP647 (formerly PF-00547659). 7. Subjects with known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients. 8. Subjects have received anti-TNF treatment within 60 days before baseline (Visit 2). 9. Subjects have received any biologic with immunomodulatory properties (other than anti-TNFs) within 90 days before baseline (Visit 2). 10. Subjects have received any nonbiologic treatment with immunomodulatory properties (other than their current background UC treatment) within 30 days before baseline (Visit 2). 11. Subjects have ever received anti-integrin/adhesion molecule treatment (eg, natalizumab, vedolizumab, efalizumab, etrolizumab, or any other investigational anti-integrin/adhesion molecule). 12. Subjects have received parenteral or rectal glucocorticoids, or rectal 5-ASA, within 14 days before screening endoscopic procedure. 13. Subjects have received leukocyte apheresis or selective lymphocyte, monocyte, or granulocyte apheresis or plasma exchange within 30 days before baseline (Visit 2). 14. Subjects have participated in other investigational studies within either 30 days or 5 half-lives of investigational product used in the study (whichever is longer) before baseline (Visit 2). 15. Subjects have received a live (attenuated) vaccine within 30 days before the baseline visit (Visit 2). 16. Subjects with active enteric infections (positive stool culture and sensitivity), Clostridium difficile infection or pseudomembranous colitis [subjects with C. difficile infection at screening may be allowed re-test after treatment], evidence of active cytomegalovirus infection or Listeria monocytogenes, known active invasive fungal infections such as histoplasmosis or parasitic infections, clinically significant underlying disease that could predispose the subjects to infections, or a history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks before the baseline visit (Visit 2). 17. Subjects with abnormal chest x-ray findings at screening (Visit 1), such as presence of active tuberculosis (TB), general infections, heart failure, or malignancy. (A chest x-ray performed up to 12 weeks before study entry [screening, Visit 1] may be used if available; documentation of the official reading must be located and available in the source documentation.) 18. Subjects with evidence of active or latent infection with Mycobacterium tuberculosis (TB) or subjects with this history who have not completed a generally accepted full course of treatment before randomization are excluded. All other subjects must have either the Mantoux (purified protein derivative [PPD]) tuberculin skin test or interferon gamma release assay (IGRA) performed. Subjects who have no history o f previously diagnosed active or latent tuberculosis are excluded if they have a positive Mantoux (PPD) tuberculin skin test (ie ≥5 mm induration) or a positive IGRA (the latter to be tested at the site’s local laboratory) during screening or within 12 weeks before randomization. If IGRA test cannot be performed locally, a central laboratory may be used, with prior agreement from the sponsor. • An IGRA is strongly recommended for subjects with a prior Bacillus Calmette-Guérin (BCG) vaccination, but may be used for any subject. Documentation of IGRA product used and the test result must be in the subject's source documentation if performed locally. Acceptable IGRA products include QuantiFERON TB Gold Plus In-Tube Test. • If the results of the IGRA are indeterminate, the test may be repeated, and if a negative result is obtained, enrollment may proceed. In subjects with no history of treated active or latent tuberculosis, a positive test on repeat will exclude the subject. Subjects with a history of active or latent tuberculosis infection must follow instructions for “Subjects with a prior diagnosis of active or latent tuberculosis are excluded unless both of the following criteria are met” in this criterion. • Subjects with repeat indeterminate IGRA results, with no prior TB history, may be enrolled after consultation with a pulmonary or infectious disease specialist who determines low risk of infection (ie, subject would be acceptable for immunosuppressant [eg, anti-TNF] treatment without additional action). This consultation must be included in source documentation. Results from a chest x-ray, taken within the 3 months before or during screening (Visit 1) must show no abnormalities suggestive of active TB infection as determined by a qualified medical specialist. Subjects with a prior diagnosis of active or latent tuberculosis are excluded unless both of the following criteria are met: • The subject has previously received an adequate course of treatment for either latent (eg, 9 months of isoniazid or an acceptable alternative regimen, in a locale where rates of primary multidrug TB resistance are <5%. Subjects from regions with higher rates of primary multidrug TB resistance are excluded) or active (acceptable multidrug regimen) TB infection. Evidence of diagnosis and treatment must be included in source documentation. Consultation with a pulmonary or infectious disease specialist to confirm adequate treatment (ie, subject would be acceptable for immunosuppressant [eg, anti-TNF] treatment without additional action) must be performed during the screening period. The consultation report must be included in source documentation prior to enrollment. • A chest x-ray performed within 3 months prior to screening (Visit 1) or during screening (Visit 1) indicates no evidence of active or recurrent disease, and documentation of interpretation by a qualified medical specialist must be included in source documentation. 19. Subjects with a pre-existing demyelinating disorder such as multiple sclerosis or new onset seizures, unexplained sensory motor, or cognitive behavioral, neurological deficits, or significant abnormalities noted during screening. 20. Subjects with any unexplained symptoms suggestive of progressive multifocal leukoencephalopathy (PML) based on the targeted neurological assessment during the screening period (see Section 7.2.3.3). 21. Subjects with a transplanted organ. Skin grafts to treat pyoderma gangrenosum are allowed. 22. Subjects with a significant concurrent medical condition at the time of screening (Visit 1) or baseline (Visit 2), including, but not limited to, the following: • Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, GI (except disease under study), endocrine, cardiovascular, pulmonary, immunologic [eg, Felty’s syndrome], or local active infection/infectious illness) that, in the investigator’s judgment will substantially increase the risk to the subject if he or she participates in the study. • Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence). • Presence of acute coronary syndrome (eg, acute myocardial infarction, unstable angina pectoris) within 24 weeks before screening (Visit 1). • History of significant cerebrovascular disease within 24 weeks before screening (Visit 1). 23. Subjects who have had significant trauma or major surgery within 4 weeks before the screening visit (Visit 1), or with any major elective surgery scheduled to occur during the study. 24. Subjects with evidence of cirrhosis with or without decompensation. 25. Subjects with primary sclerosing cholangitis. 26. Subjects with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). NOTE: if a subject tests negative for HBsAg, but positive for HBcAb, the subject would be considered eligible if no presence of HBV DNA is confirmed by HBV DNA PCR reflex testing performed in the central laboratory. 27. Subjects with chronic hepatitis C (HCV) (positive HCVAb and HCVRNA). Note: Subjects who are HCVAb positive without evidence of HCVRNA may be considered eligible (spontaneous viral clearance or previously treated and cured [defined as no evidence of HCVRNA at least 12 weeks prior to baseline]). 28. Subjects with any of the following abnormalities in hematology and/or serum chemistry profiles during screening. NOTE: Screening laboratory tests, if the results are considered by the investigator to be transient and inconsistent with the subject’s clinical condition, may be repeated once during the screening period for confirmation. Results must be reviewed for eligibility prior to the screening endoscopy procedure. • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≥ 3.0 × the upper limit of normal (ULN). • Total bilirubin level ≥1.5 ×ULN or >2.0×ULN if the subject has a known documented history of Gilbert’s syndrome. • Hemoglobin level ≤ 80 g/L (8.0 g/dL). • Platelet count ≤ 100 × 1 000 000 000/L (100,000 cells/mm3) or ≥1000 × 1 000 000 000/L (1,000,000 cells/mm3).* • White blood cell count ≤ 3.5 × 1 000 000 000/L (3500 cells/mm3). • Absolute neutrophil count (ANC) <2 × 1 000 000 000/L (2000 cells/mm3). • Serum creatinine level >1.5× ULN or estimated glomerular filtration rate <30 mL/min/1.73 m2 based on the abbreviated Modification of Diet in Renal Disease Study Equation. *Note: If platelet count is <150,000 cells/mm3, a further evaluation should be performed to rule out cirrhosis, unless another etiology has already been identified. 29. Subjects with known human immunodeficiency (HIV) infection based on documented history, with positive serological test, or positive HIV serologic test at screening, tested at the site's local laboratory in accordance with country requirements or tested at the central laboratory. Note: A documented negative HIV test within 6 months of screening is acceptable and does not need to be repeated. 30. Subjects who have, or who have a history of (within 2 years before screening [Visit 1]), serious psychiatric disease, alcohol dependency, or substance/drug abuse or dependency of any kind, including abuse of medical marijuana (cannabis). 31. Subjects with any other severe acute or chronic medical or psychiatric condition or laboratory or electrocardiogram (ECG) abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 32. Female subjects who are planning to become pregnant during the study period. 33. Subjects who do not agree to postpone donation of any organ or tissue, including male subjects who are planning to bank or donate sperm and female subjects who are planning to harvest or donate eggs, for the duration of the study and through 16 weeks after last dose of investigational product. 34. Subjects who are investigational site staff members or relatives of those site staff members or subjects who are Shire employees directly involved in the conduct of the study.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Placebo
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
No
Name of IMP
Ontamalimab (SHP647)
Type of IMP
Immunological
Pharmaceutical class
IgG2 monoclonal antibody
Therapeutic indication
Ulcerative Colitis
Therapeutic benefit
SHP647, in doses of 7.5 mg, 22.5 mg, and 75 mg, appears to increase the rate of remission in subjects with UC.
Biospecimen retention
Samples without DNA
Biospecimen description
Target sample size
12
Actual enrollment target size
Date of first enrollment: Type
Actual
Date of first enrollment: Date
01/11/2019
Date of study closure: Type
Actual
Date of study closure: Date
10/12/2020
Recruitment status
Other
Recruitment status: Specify
Study is not initiated yet
Date of completion
IPD sharing statement plan
No
IPD sharing statement description
Not decided yet
Additional data URL
NA
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
No Numbers
No Numbers
Sources of Monetary or Material Support
Name
Shire Human Genetic Therapies, Inc. ("Shire")
Secondary Sponsors
Name
None
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Aziz
Zoghbi
MCT Lebanon s.a.r.l.
Lebanon
01-- 612500 ext2040
zog_Az@ct-CRO.com
CRO
Scientific
Shire Human Genetic Therapies, Inc.
US
300 Shire Way Lexington Post code MA 02421
United States of America
+1 781 482 0852
chantal.letourneau@shire.com
sponsor "Clinical Trial Information Desk"
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Rafik Hariri University Hospital
Dr. Iyad Issa
Gastroenterology
Approved
Al Zahraa University Hospital
Dr. Mahmoud Hallal
Gastroenterology
NA
Hammoud Hospital University Medical Center
Dr. Hassan Atwi
Gastroenterology
Approved
Hammoud Hospital University Medical Center
Dr. Majed Bahlawan
Gastroenterology
Approved
Hotel Dieu De France
Dr. Cesar Yaghi
Gastroenterology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Rafic Hariri University Hospital
29/05/2019
Abir Sinno
abir.sinno@crurhuh.com
+961 1 830000 ext 2037
Hotel Dieu de France
06/06/2019
Virginia El Khoury
Virginia.elkhoury@usj.edu.lb
+961 1 421229
Hammoud Hospital University Medical Center
15/07/2019
ghada aoun
medical@hammoudhospital.org
+9617721021
Countries of Recruitment
Name
Lebanon
Belgium
Bulgaria
Estonia
France
Greece
Hungary
Ireland
Slovakia
Portugal
Spain
Argentina
Bosnia and Herzegovina
Canada
Colombia
Japan
Mexico
Democratic People Republic of Korea
Switzerland
Ukraine
United States of America
Health Conditions or Problems Studied
Condition
Code
Keyword
Ulcerative Colitis
Ulcerative colitis (K51)
Ulcerative Colitis
Interventions
Intervention
Description
Keyword
SHP647 25 mg
SHP647 will be administered subcutaneously in a PFS 1ml
randomization ratio: 2:2:1 for SHP647 25mg, 75mg and Placebo respectively
SHP647 75 mg
SHP647 will be administered subcutaneously in a PFS 1ml
randomization ratio: 2:2:1 for SHP647 25mg, 75mg and Placebo respectively
Placebo
The placebo solution will contain the same sterile aqueous buffered solution as the test product but will not contain SHP647
randomization ratio: 2:2:1 for SHP647 25mg, 75mg and Placebo respectively
Primary Outcomes
Name
Time points
Measure
Remission is defined as a composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy as follows: • stool frequency subscore of 0 or 1 with at least a 1-point change from baseline AND • rectal bleeding subscore of 0 AND • endoscopic subscore of 0 or 1 (modified, excludes friability).
Week 12
Remission at week 12
Key Secondary Outcomes
Name
Time points
Measure
Endoscopic remission, as defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability)
Week 12
Endoscopic remission at week 12
Clinical remission, as defined by stool frequency subscore of 0 or 1 with at least a 1-point change from baseline in stool frequency subscore, and rectal bleeding subscore of 0
Week 12
Clinical remission at week 12
Clinical response based on composite score. It is defined as a decrease from baseline in the composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding ≥1 point or a subscore for rectal bleeding ≤1.
Week 12
Clinical response at week 12
Mucosal healing based on endoscopic and histological assessment. it s defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of ≤2.
Week 12
Mucosal Healing at week 12
Remission, defined as a total Mayo score ≤2 with no individual subscore (stool frequency, rectal bleeding, endoscopy [modified, excludes friability], and physician’s global assessment) exceeding 1
Week 12
Remission at week 12
Clinical response based on total Mayo score. Clinical response (Mayo) is defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding ≥1 point or a subscore for rectal bleeding ≤1.
Week 12
Clinical response based on Mayo score at week 12
Partial Mayo score ≤2 with no individual subscore >1. The partial Mayo score does not include the endoscopy subscore.
Weeks 4, 8 and 12
Partial Mayo score at weeks 4, 8 and 12
Clinical remission as defined by stool frequency subscore of 0 or 1 with at least a 1-point change from baseline in stool frequency subscore, and rectal bleeding subscore of 0.
weeks 4 and 8
Clinical Remission at weeks 4 and 8
Endoscopic remission with endoscopic subscore of 0.
Week 12
Endoscopic Remission at week 12
Clinical remission with both rectal bleeding and stool frequency subscores of 0.
Weeks 4, 8 and 12
Clinical remission at Weeks 4, 8 and 12
Deep remission. It is defined as both endoscopic and rectal bleeding subscores of 0, and stool frequency subscore ≤1 and a centrally read Geboes score of ≤2.
Week 12
Deep remission at Week 12
Change in abdominal pain, urgency and diarrhea item scores, absolute stool frequency, absolute rectal bleeding and total sign/symptom score based on subject daily e-diary entries (sum of rectal bleeding, stool frequency, abdominal pain, diarrhea, and urgency).
Week 0 and Week 12
Week 0 and Week 12
Change from baseline in IBDQ domain and total (absolute) scores ).
Week 0, Week 8, up to Week 12, or early termination
Change in IBDQ and total scores Week 0, Week 8, up to Week 12, or early termination
Change in SF-36, version 2, acute (physical and mental component summary scores and individual domain scores).
From Baseline to the Week 12/ET visit
Change in SF-36, version 2, acute (physical and mental component summary scores and individual domain scores).
Incidence of all-cause hospitalizations and total inpatient days.
From Baseline to week 12
Incidence of all-cause hospitalizations and total inpatient days.
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial